Studies of differentiation of specific cell types are of fundamental importance to an understanding of developmental biology. Studies of the differentiation of the type II pneumocyte of the lung are particularly relevant to an understanding of the pathophysiology of the respiratory distress snydrome of the newborn and its possible treatment by pharmacologic agents which affect maturation of type II pneumocytes. In order to completely study the differentiation of type II pneumocytes, its precursor cells must be obtained. Because their properties are not known, there are no direct means by which such cells can be isolated. This investigation proposes an indirect approach to isolation of precursor cells of type II pneumocytes. The approach is based on the fact that cells express a sequential pattern of surface antigens during the process of differentiation. These differentiation antigens of type II pneumocytes will be characterized on differentiated cells and on cells during the process of differentiation. The antigens will be identified by monoclonal antibodies produced in mice. The monoclonal antibodies will be labelled for detection in a laser flow cytometer cell sorter. Using techniques of laser flow cytometry for detection of specific complements of surface components, as well as for detection of lamellar body structures, progressively less differentiated populations of type II pneumocytes will be isolated from fetal rabbit lungs until precursor cells of type II pneumocytes are identified and isolated. The precursor status of cells will be established by demonstrating differentiation into type II pneumocytes in cell culture. Once isolated, identifiable properties of precursor cells may allow their subsequent isolation by different techniques. The successful completion of these studies would make available precursor cells of type II pneumocytes to study the hormonal regulation of their development so that rational, relatively safe pharmacologic therapies might be developed for prevention of the respiratory distress syndrome.